The goal of the project is to investigate the biological roles of members of the chemokine family of cytokines by studying chemokine actions in vivo, primarily in animal models of infectious disease. This laboratory discovered two mouse chemokines, Crg-2 and Mig. Crg-2 is the mouse homologue of the human chemokine IP-10, and the murine Mig (MuMig) was used to identify a human homologue, HuMig. Crg-2/IP-10 and Mig are related interferon-gamma inducible chemokines that preferentially target T lymphocytes, acting as chemotactic factors for activated T cells. It is our hypothesis that these chemokines are important for recruiting T cells to sites of inflammation and immune response. Infections of mice with intracellular pathogens, including malaria, Toxoplasma gondii and vaccinia virus, led to widespread induction of mig and crg-2. We demonstrated that inductions of mig by infection with T. gondii and vaccinia virus were dependent absolutely on interferon gamma expression patterns of mig and crg-2/IP-10 differed. In each model the highest level of expression of mig was in the liver while crg-2 was expressed at the highest level in different tissues concordant with the local expression of interferon-gamma. These finding suggest that the actions of Mig may extend beyond local sites of inflammation. We analyzed expression of 16 mouse chemokines in granulomatous inflammation using eggs of the parasite Schistosoma mansoni in a sensitization and challenge protocol where responses were manipulated by co-administration of IL-12 during sensitization. We found significant differences in chemokine gene expression in the lungs of mice challenged with eggs of S. mansoni following sensitization in the presence of italis-12 as compared to sensitization without IL-12. Following sensitization in the presence of IL-12, mig and crg-2 were the most highly induced chemokine genes, suggesting that these chemokines might have a role in the anelioration of granulomatous pathology seen in these mice. In order to evaluate the roles of mig and crg-2/IP-10 in host defence we have produced recombinant vaccinia virus producing these chemokines, neutralizing antibodies, and mice with targeted deletion/disruption of the mig gene and studies using these biological reagents are underway.